title: Amine-reactive OVA multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for GCP-2 in L. major infection.
abstract: Anticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. We here describe a two-step procedure based on the use of OVA multimers purified by size exclusion chromatography after incubation with glutaraldehyde at pH 6. When such polymers are incubated with a target protein at pH 8.5 to deprotonate reactive amines, complexes are formed that confer immunogenicity to self-antigens. The chemokine GCP-2/CXCL6, the cytokines GM-CSF, IL-17F, IL-17E/IL-25, IL-27, and TGF-β1, and the MMP-9/gelatinase B are discussed as examples. mAb, derived from such immunized mice, have obvious advantages for in vivo studies of the target proteins. Using a mAb against GCP-2, obtained by the method described here, we provide the first demonstration of the major role played by this chemokine in rapid neutrophil mobilization after Leishmania major infection. Pre-activated OVA multimers reactive with amine residues thus provide an efficient carrier for auto-vaccination against 9-90 kDa autologous proteins.
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Uyttenhove
authors.forename: Reece G
authors.initials: RG
authors.lastname: Marillier
authors.forename: Fabienne
authors.initials: F
authors.lastname: Tacchini-Cottier
authors.forename: Mélanie
authors.initials: M
authors.lastname: Charmoy
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Caspi
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Damsker
authors.forename: Stanislas
authors.initials: S
authors.lastname: Goriely
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
authors.forename: Sofie
authors.initials: S
authors.lastname: Struyf
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Jacques
authors.initials: J
authors.lastname: Van Snick
mesh_terms: D000588:Amines / Q000737:chemistry*; D000818:Animals; D002465:Cell Movement; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D005976:Glutaral / Q000378:metabolism; D007114:Immunization; D020381:Interleukin-17 / Q000502:physiology; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000276:immunology*; D009504:Neutrophils; D010047:Ovalbumin / Q000276:immunology*; D055503:Protein Multimerization
chemical_list: D000588:Amines; D018925:Chemokines; D016207:Cytokines; D020381:Interleukin-17; D008869:Microtubule-Associated Proteins; D010047:Ovalbumin; D005976:Glutaral